The overall goal of this research is to elucidate the various functions of the extracellular calcium sensing receptor gene (CaR) in the many tissues in which it is expressed. Mice that are homozygous for a null mutation of the CaR gene die within 20 days of birth due to hyperparathyroidism and severe hypercalcemia. The specific goal of this research proposal is to develop a healthy mouse model that is homozygous for a null mutation of the CaR gene. The hypercalcemia in these mice is known to be due, at least in part, to the inability of these mice to properly regulate parathyroid hormone (PTH) secretion from the parathyroid gland. Therefore, it is hypothesized that targeted expression of a transgene containing the CaR to the parathyroid gland will be sufficient to maintain proper PTH and calcium levels in mice lacking CaR expression in all other tissues and thus rescue them from early death.